Overexpression of hypoxia-inducible-factor 1α(HIF-1α) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage

Abstract

The purpose of this study is to investigate the clinical and histopathologic significance of hypoxia-inducible-factor 1a (HIF-1a) expression in oesophageal squamous cell carcinoma. One hundred and thirty surgically resected specimens of OSCC were immunohistochemically assessed for HIF-1a expression with monoclonal antibody. High HIF-1a immunostaining was detected in 40 specimens . The percentage of high HIF-1a expression cases increased with tumour stage according to pTNM system. High HIF-1a expression correlated with pTNM stage , depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion and positive surgical margin. The overall survival rate was worse in patients with high HIF-1a pattern than in patients with low-expression pattern. Univariate analyses identified high HIF-1a positivity, depth of tumour invasion, lymph node metastasis, distant metastasis, lymphatic invasion, and a positive surgical margin as risk factors. Multivariate analyses indicated that depth of tumour invasion, lymph node metastasis and positive surgical margin, but not HIF-1a, were independent prognostic factors. Survival in patients with a high HIF-1a expression was significantly worse than in those with low expression in patient treated with adjuvant therapy.

The relation between hypoxia‐inducible factor (HIF)‐1α and HIF‐2α expression with anemia and outcome in surgically treated head and neck cancer

“…6 Both HIF-1a and HIF-2a, which are part of the nuclear transcriptional response to hypoxia, demonstrated a high degree of correlation, as reported previously in patients with HNSCC. 20 HIF-1a expression also was correlated with disease stage, a finding that also has been reported in patients with esophageal squamous cell carcinomas, 30 and reflects an aggressive phenotype. However, HIF-2a expression did not correlate with disease stage, suggesting that there is not a simple relation between HIF-2a expression and disease behavior.…”

“…More recent studies have stratified the degree of staining based on the degree of reactivity. 19,24,30 In addition, in the current study, a higher proportion of patients received postoperative RT (85%) compared with the original study (35%). The contradictory findings between the 2 studies, thus, may be explained in part by design differences, larger patient numbers, and the longer follow-up available for patients from the original study.…”

“…20,24 In addition, in patients with esophageal, nasopharyngeal, and cervical tumors who received treatment with a variety of modalities, HIF-1a expression has been correlated with a poor outcome. 19,30,34 Although HIF-2a expression has been used as a marker of tumor hypoxia, there is equivocal evidence linking its expression with clinical outcome. Whereas it has been shown to be an independent indicator of survival in patients with HNSCC 20 and patients with early-stage nonsmall cell lung cancers 35 , other studies in patients with HNSCC and nasopharyngeal cancers have found that HIF-2a does not correlate with outcome.…”

HIF-1α determines the metastatic potential of gastric cancer cells

“…Hypoxia-inducible factor 1a expression has been shown in a vast array of human carcinomas and their metastases by means of immunohistochemistry (Zhong et al, 1999). For breast, colorectal, invasive cervical and squamous cell oesophageal cancer a positive correlation between tumoural HIF-1a expression and prognosis has been shown (Birner et al, 2000;Bos et al, 2003;Kurokawa et al, 2003;Kuwai et al, 2003).…”

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

“…18 Tumor hypoxia has been associated with several aspects of aggressive tumor behaviour including: increased invasiveness and proliferation, 19,20 the formation of metastasis and poor patient survival. 21,22 In addition, hypoxia has also been shown to contribute to genomic instability through the clonal selection of cells that carry gene mutations, for example cells that are p53 mutant. [23][24][25] Significantly, hypoxic cells are highly resistant to radiation [26][27][28] and chemotherapy.…”